Project Abstract: Hepatitis B (HBV) affects over 1.25 million Americans, and hepatitis C (HCV) over 3.2 million Americans. In the decades to come, more than 150,000 Americans are expected to die from these conditions unless steps are taken to increase awareness, diagnosis, and access to necessary care and treatment. Emerging interferon-free, direct-acting all-oral antiviral (DAA) treatments have changed the landscape of HCV treatment and care. These treatments appear to be safer than interferon-based treatments and provide exceptionally high rates of sustained virological response (SVR). Both HBV and HCV treatment guidelines have been updated to reflect evidence regarding initiation of new therapies; however, the evidence for those recommendations is largely based on clinical trials conducted under highly controlled conditions in restricted patient populations with limited data collection. Significant health disparities?across race, sex, age, and co-infection (with HIV or dual hepatitis)?may limit the generalizability of these populations. Data from longitudinal cohorts of ?real world? hepatitis patients are needed to assess the population impact of rapidly evolving antiviral therapies, to understand the spectrum of disease and its natural history, and to evaluate the public health impact of chronic viral hepatitis. The Chronic Hepatitis Cohort Study (CHeCS) is the first comprehensive longitudinal cohort study of chronic viral hepatitis in the US, and has served as a model platform for observational data collection in this population. Since 2010, CHeCS has reported valuable information and expanded knowledge on many facets of hepatitis disease and policy. We propose to build upon CHeCS to develop ?CHeCS-II,? in order to achieve the long-term goal of applying this rich data and infrastructure resource to inform public health planning, policy decisions, and clinical management of HBV and HCV. To achieve this, we will leverage the established CHeCS infrastructure, which has: (1) a diverse, real-world, non-veteran-based US cohort of >3,000 HBV, >11000 HCV, and >500 HIV co-infected patients receiving care through four U.S. health systems; (2) an experienced multidisciplinary team; (3) an efficient system for patient identification and data collection. We will provide scientific leadership to identify research findings and priorities by: (1) Offering seamless collaboration across study sites and with the Centers for Disease Control (Aim 1); (2) Expanding our HCV cohort to over 14,000 patients with >2 years' follow-up; (3) Increasing follow-up of HBV patients to >5 years; (4) Collecting additional data regarding social determinants of health, including access to and uptake of care (Aim 2); (5) Applying rigorous analytical approaches to develop an in-depth understanding of health disparities and comorbidities, as well as investigating how these differences impact access to and uptake of antiviral therapy; (6) Advancing translation of this research to inform hepatitis-related policy and practice (Aim 3).